Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs

196 Pages·2010·1.16 MB·English

RHefeearletnhc Teeschnology Assessment 2010; Vol. 14: No.17
Health Technology Assessment 2010; Vol. 14: No. 17
AApbpsetnrdaicxt 1
GSloesasarcryh strategy
List of abbreviations
Appendix 2
Glowsisnabruyg asn cdo ldisets of abbreviations
AEpxpeecnudtiixve 3 s ummary
BaEcxkcgluroduendd studies
Objectives
ApMpeenthdoixd s4
ReDsruultgs regimens
Paracetamol and selective and
Conclusions
ApIpmepnldicixat 5io ns for health care
non-selective non-steroidal anti-
ReVcaolimdimtye nadssaetisosnms efnotr research
inflammatory drugs (NSAIDs) for the
ACphpaepntdeirx 16
reduction of morphine-related side NBeatcwkogrrko utanbdles
Morphine
effects after major surgery: ApPpaernacdeixta 7m ol
NAond-dsitteiroonidala lt aabnltei-si nfoflra msemnsaittoivryit yd raungasl y(NseSsAIDs) and cyclo-oxygenase 2 (COX-2) inhibitors
a systematic review
Previous systematic reviews
ApDpeefinndiitxio 8n of decision problem
TMhei xsecodp ter eoaf ttmhee nretv cieowmparison analyses for additional morphine-related outcomes
ACphpaepntdeirx 29
C McDaid, E Maund, S Rice, K Wright, DMateat heoxdtrsaction
Search strategy
B Jenkins and N Woolacott
Inclusion and exclusion criteria
Data extraction
Study quality
Methods for synthesis
Chapter 3
Results
Quantity and quality of research available
Study characteristics
Study quality
Assessment of effectiveness
Chapter 4
Discussion
Principal findings
Consistency with direct comparisons
Strengths and limitations of the assessment
Chapter 5
Conclusions
Implications for service provision
Suggested research priorities
March 2010
Acknowledgements
10.3310/hta14170
Contribution of authors
Health Technology Assessment
NIHR HTA programme
www.hta.ac.uk
HTA
How to obtain copies of this and other HTA programme reports
An electronic version of this title, in Adobe Acrobat format, is available for downloading free of charge for
personal use from the HTA website (www.hta.ac.uk). A fully searchable DVD is also available (see below).
Printed copies of HTA journal series issues cost £20 each (post and packing free in the UK) to both
public and private sector purchasers from our despatch agents.
Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is
£2 per issue and for the rest of the world £3 per issue.
How to order:
– fax (with credit card details)
– post (with credit card details or cheque)
– phone during office hours (credit card only).
Additionally the HTA website allows you to either print out your order or download a blank order form.
Contact details are as follows:
Synergie UK (HTA Department) Email: [email protected]
Digital House, The Loddon Centre
Tel: [phone] – ask for ‘HTA Payment Services’
Wade Road (out-of-hours answer-phone service)
Basingstoke
Hants RG24 8QW Fax: [phone] – put ‘HTA Order’ on the fax header
Payment methods
Paying by cheque
If you pay by cheque, the cheque must be in pounds sterling, made payable to University of Southampton
and drawn on a bank with a UK address.
Paying by credit card
You can order using your credit card by phone, fax or post.
Subscriptions
NHS libraries can subscribe free of charge. Public libraries can subscribe at a reduced cost of £100 for
each volume (normally comprising 40–50 titles). The commercial subscription rate is £400 per volume
(addresses within the UK) and £600 per volume (addresses outside the UK). Please see our website for
details. Subscriptions can be purchased only for the current or forthcoming volume.
How do I get a copy of HTA on DVD?
Please use the form on the HTA website (www.hta.ac.uk/htacd/index.shtml). HTA on DVD is currently free
of charge worldwide.
The website also provides information about the HTA programme and lists the membership of the v arious
committees.
Paracetamol and selective and
non-selective non-steroidal anti-
inflammatory drugs (NSAIDs) for the
reduction of morphine-related side
effects after major surgery:
a systematic review
C McDaid,* E Maund, S Rice, K Wright,
B Jenkins and N Woolacott
Centre for Reviews and Dissemination, University of York, York, UK
*Corresponding author
Declared competing interests of authors: none
Published March 2010
10.3310/hta14170
This report should be referenced as follows:
McDaid C, Maund E, Rice S, Wright K, Jenkins B, Woolacott N. Paracetamol and selective
and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the reduction of
morphine-related side effects after major surgery: a systematic review. Health Technol Assess
2010;14(17).
Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE, Excerpta
Medica/EMBASE, Science Citation Index Expanded (SciSearch) and Current Contents/Clinical
Medicine.
NIHR Health Technology Assessment programme
The Health Technology Assessment (HTA) programme, part of the National Institute for Health
Research (NIHR), was set up in 1993. It produces high-quality research information on the
effectiveness, costs and broader impact of health technologies for those who use, manage and provide care
in the NHS. ‘Health technologies’ are broadly defined as all interventions used to promote health, prevent
and treat disease, and improve rehabilitation and long-term care.
The research findings from the HTA programme directly influence decision-making bodies such as the
National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee
(NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they
form a key component of the ‘National Knowledge Service’.
The HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three
routes to the start of projects.
First is the commissioned route. Suggestions for research are actively sought from people working in the
NHS, from the public and consumer groups and from professional bodies such as royal colleges and NHS
trusts. These suggestions are carefully prioritised by panels of independent experts (including NHS service
users). The HTA programme then commissions the research by competitive tender.
Second, the HTA programme provides grants for clinical trials for researchers who identify research
questions. These are assessed for importance to patients and the NHS, and scientific rigour.
Third, through its Technology Assessment Report (TAR) call-off contract, the HTA programme
commissions bespoke reports, principally for NICE, but also for other policy-makers. TARs bring together
evidence on the value of specific technologies.
Some HTA research projects, including TARs, may take only months, others need several years. They
can cost from as little as £40,000 to over £1 million, and may involve synthesising existing evidence,
undertaking a trial, or other research collecting new data to answer a research problem.
The final reports from HTA projects are peer reviewed by a number of independent expert referees before
publication in the widely read journal series Health Technology Assessment.
Criteria for inclusion in the HTA journal series
Reports are published in the HTA journal series if (1) they have resulted from work for the HTA
programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and
editors.
Reviews in Health Technology Assessment are termed ‘systematic’ when the account of the search, appraisal
and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication
of the review by others.
The research reported in this issue of the journal was commissioned by the HTA programme as project
number 08/114/01. The contractual start date was in February 2009. The draft report began editorial
review in August 2009 and was accepted for publication in October 2009. As the funder, by devising a
commissioning brief, the HTA programme specified the research question and study design. The authors
have been wholly responsible for all data collection, analysis and interpretation, and for writing up their
work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would
like to thank the referees for their constructive comments on the draft document. However, they do not
accept liability for damages or losses arising from material published in this report.
The views expressed in this publication are those of the authors and not necessarily those of the HTA
programme or the Department of Health.
Editor-in-Chief: Professor Tom Walley CBE
Series Editors: Dr Martin Ashton-Key, Dr Aileen Clarke, Professor Chris Hyde,
Dr Tom Marshall, Dr John Powell, Dr Rob Riemsma and Professor Ken Stein
ISSN 1366-5278
© 2010 Queen’s Printer and Controller of HMSO
This journal may be freely reproduced for the purposes of private research and study and may be included in professional journals provided that
suitable acknowledgement is made and the reproduction is not associated with any form of advertising.
Applications for commercial reproduction should be addressed to: NETSCC, Health Technology Assessment, Alpha House, University of
Southampton Science Park, Southampton SO16 7NS, UK.
Published by Prepress Projects Ltd, Perth, Scotland (www.prepress-projects.co.uk), on behalf of NETSCC, HTA.
Printed on acid-free paper in the UK by Henry Ling Ltd, The Dorset Press, Dorchester. G
DOI: 10.3310/hta14170 Health Technology Assessment 2010; Vol. 14: No. 17
Abstract
Paracetamol and selective and non-selective non-
steroidal anti-inflammatory drugs (NSAIDs) for the
reduction of morphine-related side effects after major
surgery: a systematic review
C McDaid,* E Maund, S Rice, K Wright, B Jenkins and N Woolacott
Centre for Reviews and Dissemination, University of York, York, UK
*Corresponding author
Objectives: To determine which class of non-opioid odds ratio (OR) and zero for mean difference (MD).
analgesics – paracetamol (acetaminophen), NSAIDs or Trials making direct comparisons between the active
COX-2 inhibitors – is the most effective at reducing interventions were also pooled in a meta-analysis
morphine consumption and associated adverse effects using a random effects model. Sensitivity analyses
when used as part of multimodal analgesia following were performed to assess the effects of study quality,
major surgery. individual drugs, and baseline morphine consumption.
Data sources: A systematic literature review was Results: Sixty relevant studies were identified. When
conducted using MEDLINE, EMBASE and CENTRAL paracetamol, NSAIDs or COX-2 inhibitors were added
databases, searched from January 2003 to February to PCA morphine, there was a statistically significant
2009 and updating an earlier review. reduction in morphine consumption: paracetamol
Review methods: Randomised controlled trials (MD –6.34 mg; 95% CrI –9.02 to –3.65); NSAIDs
comparing paracetamol, NSAIDs or COX-2 inhibitors (MD –10.18; 95% CrI –11.65 to –8.72); and COX-
to each other or placebo, in adults receiving patient- 2 inhibitors (MD –10.92; 95% CrI –12.77 to –9.08).
controlled analgesia (PCA) with morphine following NSAIDs and COX-2 inhibitors were both significantly
major surgery, were included. The COX-2 inhibitors better than paracetamol, and there was no significant
rofecoxib and valdecoxib were excluded. Only trials difference between NSAIDs and COX-2 inhibitors (MD
that reported 24-hour morphine consumption were –0.74; 95% CrI –3.03 to 1.56). There was a significant
included. Other outcomes of interest were morphine- reduction in nausea and PONV with NSAIDs compared
related adverse effects and adverse effects related to placebo (OR 0.70; 95% CrI 0.53 to 0.88) but not
to the non-opioids. Adequacy of randomisation, for paracetamol or COX-2 inhibitors, nor for NSAIDs
concealment of allocation, double blinding, and the compared to paracetamol or COX-2 inhibitors.
flow of patients within the trial was assessed. The main Conclusions: 24-hour morphine consumption
analysis was a mixed treatment comparison (MTC) decreased by 6.3 mg to 10.9 mg, compared to placebo,
evaluating the relative effects of the four treatment when paracetamol, NSAID or COX-2 inhibitors were
classes. Four main outcomes were prioritised: 24-hour added to PCA morphine following surgery. Differences
morphine consumption, sedation, nausea and vomiting, in effect between the three drug classes were small
and surgical bleeding. Studies reporting nausea alone and unlikely to be of clinical significance. There does
were pooled with studies reporting postoperative not appear to be a strong case for recommending
nausea and vomiting (PONV). Comparisons were routine addition of any of the three non-opioids to PCA
described as statistically significant (at 5% level) morphine in the 24 hours immediately after surgery, or
when the credibility interval (CrI) did not cross 1 for for favouring one drug class above the others.
iii
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.

DOI: 10.3310/hta14170 Health Technology Assessment 2010; Vol. 14: No. 17
Contents
Glossary and list of abbreviations ........... vii 5 Conclusions ............................................... 39
Implications for service provision ............. 39
Executive summary ................................. ix Suggested research priorities ..................... 39
1 Background ............................................... 1 Acknowledgements .................................. 41
Morphine ................................................... 1
Paracetamol ............................................... 2 References ................................................ 43
Non-steroidal anti-inflammatory drugs
(NSAIDs) and cyclo-oxygenase 2 Appendix 1 Search strategy ...................... 55
(COX-2) inhibitors ................................. 2
Previous systematic reviews ........................ 3 Appendix 2 winbugs codes ....................... 63
Definition of decision problem .................. 5
The scope of the review ............................. 5 Appendix 3 Excluded studies ................... 67
2 Methods .................................................... 7 Appendix 4 Drug regimens ...................... 75
Search strategy ........................................... 7
Inclusion and exclusion criteria ................. 7 Appendix 5 Validity assessment ............... 77
Data extraction .......................................... 8
Study quality .............................................. 8 Appendix 6 Network tables ...................... 79
Methods for synthesis ................................ 8
Appendix 7 Additional tables for
3 Results ....................................................... 13 sensitivity analyses ..................................... 87
Quantity and quality of research
available ................................................. 13 Appendix 8 Mixed treatment comparison
Study characteristics .................................. 14 analyses for additional morphine-related
Study quality .............................................. 21 outcomes .................................................... 89
Assessment of effectiveness ........................ 21
Appendix 9 Data extraction ..................... 93
4 Discussion ................................................. 33
Principal findings ...................................... 33 Health Technology Assessment reports
Consistency with direct comparisons ......... 34 published to date ...................................... 155
Strengths and limitations of the
assessment ............................................. 34 Health Technology Assessment
programme ............................................... 177
v
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.

DOI: 10.3310/hta14170 Health Technology Assessment 2010; Vol. 14: No. 17
Glossary and list of abbreviations
Glossary
95% credibility interval From the Bayesian Opioid Drug having morphine-like action.
approach. There is a 95% probability that the
true treatment effect (odds ratio) lies within the Patient-controlled analgesia Small doses
interval. of analgesic drugs are administered via an
intravenous pump controlled by the patient.
Mixed treatment comparison This is an When the patient presses a hand-held button a
extension of a traditional meta-analysis. pre-set dose (bolus) of the analgesic is delivered.
Whereas a traditional meta-analysis includes The administered dose is limited by setting both
only trials making direct comparisons between the dose and the time interval between doses.
an intervention and comparator, a mixed
treatment comparison analysis also includes Pruritus Itching.
indirect evidence. This approach overcomes the
limitations of the traditional approach in cases Respiratory depression The rate and/or
where there are no or limited trials making the depth of respiration is insufficient to maintain
relevant head-to-head comparison. adequate gas exchange in the lungs.
Morphine Opioid used for the relief of severe
postoperative pain.
List of abbreviations
AE adverse event NSAID non-steroidal anti-inflammatory
drug
CI confidence interval
OR odds ratio
COX cyclo-oxygenase
PCA patient-controlled analgesia
CrI credibility interval (also known
as credible interval) PONV postoperative nausea and
vomiting
DIC deviance information criterion
RCT randomised controlled trial
GI gastrointestinal
RD residual deviance
i.m. intramuscular
RR risk ratio or relative risk
IQR interquartile range
SD standard deviation
i.v. intravenous
SE standard error
MD mean difference
MTC mixed treatment comparison
All abbreviations that have been used in this report are listed here unless the abbreviation is well
known (e.g. NHS), or it has been used only once, or it is a non-standard abbreviation used only in
figures/tables/appendices, in which case the abbreviation is defined in the figure legend or in the
notes at the end of the table.
vii
© 2010 Queen’s Printer and Controller of HMSO. All rights reserved.